Sodium Carbonate → 3-(7-(3,4,5-Trimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide

HRID 1410107

반응식

HRID 1410107 반응식
Cl[C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=2)[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=2)[C:35]([NH2:37])=[O:36])O1.C([O-])([O-])=O.[Na+].[Na+]>O.O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:23][O:22][C:14]1[CH:13]=[C:12]([NH:11][C:4]2[C:5]3[N:10]=[CH:9][S:8][C:6]=3[N:7]=[C:2]([C:32]3[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=3)[C:35]([NH2:37])=[O:36])[N:3]=2)[CH:17]=[C:16]([O:18][CH3:19])[C:15]=1[O:20][CH3:21]

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 27605873-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 866717915-chloro-N-(3,4,5-trimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine

생성물 1

HCID 665503423-(7-(3,4,5-Trimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide수율 28.9%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
97 °C

실험 절차

To a stirred solution of 5-chloro-N-(3,4,5-trimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine (337 mg, 0.95 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (190 mg, 1.15 mmol) and Na2CO3 (347 mg, 3.27 mmol) in 2 mL of water and 50 mL of dioxane was added Pd(PPh3)4 (100 mg, 0.086 mmol) in one portion at room temperature under nitrogen. Then the mixture was stirred at 97° C. for 16 hours under nitrogen. The solvent was evaporated at 40° C. at reduced pressure and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (1:2)) to give a crude product. It was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 3-(7-(3,4,5-trimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide (120 mg, 27.4%) as a solid. 1H NMR (300 MHz, DMSO): δ 10.10 (s, 1H), 9.43 (s, 1H), 8.93 (s, 1H), 8.58 (d, 1H, J=8.1 Hz), 8.03-8.00 (m, 2H), 7.65-7.60 (m, 3H), 7.50 (brs, 1H), 3.87 (s, 3H), 3.71 (s, 3H), 3.30 (s, 3H). LC-MS: 438 [M+H]+, tR=1.43 min. HPLC: 99.77% at 214 nm, 99.84% at 254 nm, tR=5.68 min.

후처리

  1. customThe solvent was evaporated at 40° C. at reduced pressure
  2. customthe residue was purified by silica gel chromatography (silica gel 200-300 mesh
  3. washeluting with a mixture of petroleum ether and ethyl acetate (1:2))
  4. customto give a crude product
  5. customIt was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  6. wait20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.

출처 및 근거

ORD 기록
ord-d311768be3b848f281f58005ea5c083b
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921383B2

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